Bicyclomycin (1) is a clinically useful antibiotic. The mechanism of action of this chemotherapeutic agent is poorly understood. In this proposal, a novel explanation for the biological activity of the drug is presented. Evidence is cited in support of these pathways. Detailed experiments are proposed to substantiate these hypotheses as well as to determine the energetics of key steps. The use of """"""""molecular sensors"""""""" is promoted as diagnostic aids in these mechanistic studies. Knowledge of which route is the correct reaction pathway in bicyclomycin mediated processes may provide the molecular basis for subsequent research in this area and allow future general drug design to proceed on a less empirical basis. A select series of biomechanistic bicyclomycin analogues are proposed as potential candidates for antimicrobial evaluation.
